The completion of the yeast genome sequence in April 1996 inaugurated the era of genome-wide exploration of gene function. The goal of this project is to produce a detailed "functional map" of the yeast genome. A great many functional attributes can naturally be mapped onto the framework that the genome sequence provides. The overarching goal is to map onto this framework any kind of information that might be useful in understanding the genome, and understanding how the static information in the genome sequence comes to life in the living organism. Most of the proposed work relies on the DNA microarray technology that was developed in this laboratory a few years ago, which provides a convenient, versatile and economical tool for investigating diverse properties of genes and DNA sequences on a genome-wide basis. Three principal projects are envisioned: 1. A comprehensive survey of global gene expression programs. The effects on expression of every yeast gene of thousands of conditions, including diverse environmental and genetic perturbations as well as endogenous genetic programs, will be determined. A systematic survey will be conducted, aimed at identifying the target genes regulated by each putative regulatory gene in the yeast genome. Computational tools, already under development, will be used to draw inferences of function from the patterns of expression of each gene, and to identify candidate cis-regulatory elements that account for the observed expression patterns. 2. A detailed map of the in vivo pattern of protein binding to the yeast genome will be developed. 3. A new microarray-based method for analyzing the consequences of dominant mutations on a genomic scale will be developed. This procedure will be applied initially to define the consequences of overexpression of each yeast gene on fitness under a diverse set of selective conditions. Throughout the course of this work, we will continue our ongoing efforts to invent and discover new ways to use DNA microarray technology and other experimental approaches to explore the genome.